The estradiol-17 ẞ as a natural estrogen has an influence on the glutathione enzymatic system of treated animals, which leads quickly to the oxidation of sulfhydryl groups. The lipophilic character of its metabolites predetermines the detoxification reactions through intracellular glutathione system of the liver. The increased activity of glutathione reductase and the high decrease in content of all sulfhydryl groups in the rat liver under the influence of 100 μg/kg dose of estradiol- 17 ẞ indicate that this hormone reacts in vivo, resulting numerous toxic hydroperoxide and carcinogen metabolites. The latter were biotransformed and detoxified by the glutathione defense system.